The role of immunoreconstitution in the management of refractory opportunistic fungal infections.

Systemic fungal infections are an increasingly important threat to immunocompromised patients. In particular, invasive disease due to Candida spp., Aspergillus spp. and other moulds is associated with high mortality rates in these patients, despite the many recent advances in antifungal chemotherapy. Recent studies examining the immunopathogenesis of these infections have provided increased insights into the relative importance of the different compartments of host immune defences for these fungi. In parallel, a number of cytokines have been discovered and studies of their involvement in antifungal host defences both in vitro and in experimental animal models of fungal infections have become possible. Due to their ability to upregulate phagocyte number and/or function, the cytokines of greatest interest are granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, interferon-gamma, interleukin-1 and tumour necrosis factor-alpha. Adjuvant use of these cytokines may be of value for some refractory fungal infections, as may reconstitution of immune response by transfusion of allogeneic phagocytes. Further evaluation of the safety and efficacy of these modalities of immunotherapy is a new and promising area for research.